We aimed to derive and validate a triage tool, based on clinical assessment alone, for predicting adverse outcome in acutely ill adults with suspected COVID-19 infection.
We undertook a mixed ...prospective and retrospective observational cohort study in 70 emergency departments across the United Kingdom (UK). We collected presenting data from 22445 people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020. The primary outcome was death or organ support (respiratory, cardiovascular, or renal) by record review at 30 days. We split the cohort into derivation and validation sets, developed a clinical score based on the coefficients from multivariable analysis using the derivation set, and the estimated discriminant performance using the validation set.
We analysed 11773 derivation and 9118 validation cases. Multivariable analysis identified that age, sex, respiratory rate, systolic blood pressure, oxygen saturation/inspired oxygen ratio, performance status, consciousness, history of renal impairment, and respiratory distress were retained in analyses restricted to the ten or fewer predictors. We used findings from multivariable analysis and clinical judgement to develop a score based on the NEWS2 score, age, sex, and performance status. This had a c-statistic of 0.80 (95% confidence interval 0.79-0.81) in the validation cohort and predicted adverse outcome with sensitivity 0.98 (0.97-0.98) and specificity 0.34 (0.34-0.35) for scores above four points.
A clinical score based on NEWS2, age, sex, and performance status predicts adverse outcome with good discrimination in adults with suspected COVID-19 and can be used to support decision-making in emergency care.
ISRCTN registry, ISRCTN28342533, http://www.isrctn.com/ISRCTN28342533.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Improving retention within randomised controlled trials is important. The effectiveness of different strategies can be assessed using a Study Within A Trial (SWAT). Previous research has shown ...personalised text message reminders improve clinic attendance rates; however, the results are mixed on improving postal questionnaire return. This SWAT aims to assess whether personalised text message reminders improve completion rates for scheduled telephone follow-ups.
This SWAT is a two-arm, multi-centre randomised controlled trial with equal allocation. The host trial was the Melatonin for Anxiety prior to General anaesthesia In Children trial (ISRCTN 18296119), where the child's caregiver was to answer a scheduled telephone follow-up 14 days post-surgery; participants for the SWAT were therefore the caregiver. Text messages were sent 24-48 h before the scheduled call and the personalised version contained the first name of the caregiver which was omitted in the non-personalised version. The primary outcome was questionnaire completion rate, defined as the proportion of caregivers successfully contacted, and completed any of the questionnaires, over the telephone within the follow-up window (day 14 + 7 days).
The SWAT included 100 of the 110 (91%) participants randomised into the host trial. Randomisation within the SWAT was equal between non-personalised (n = 50) and personalised (n = 50) interventions. The overall questionnaire response rate was 73% with a difference between the two interventions of 68% in the non-personalised text message arm and 78% in the personalised text message arm. The adjusted absolute risk difference was 7.1% (95% confidence interval = -10.2%, 24.4%). There was no difference in either the time to response or the number of contact attempts between the two interventions.
There is some evidence that personalised text messages could be effective at increasing response rates when data is collected via telephone and in a population of caregivers for paediatric trial participants. However, similar SWATs have shown mixed results. Given the low-cost and low risks associated with personalising text message reminders, this SWAT could be implemented easily in other RCTs scheduling telephone follow-up appointments.
ISRCTN 18296119 , SWAT 35 (MRC Northern Ireland Network for Trials Methodology Network).
Hospital emergency departments play a crucial role in the initial assessment and management of suspected COVID-19 infection. This needs to be guided by studies of people presenting with suspected ...COVID-19, including those admitted and discharged, and those who do not ultimately have COVID-19 confirmed. We aimed to characterise patients attending emergency departments with suspected COVID-19, including subgroups based on sex, ethnicity and COVID-19 test results.
We undertook a mixed prospective and retrospective observational cohort study in 70 emergency departments across the United Kingdom (UK). We collected presenting data from 22445 people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020. Outcomes were admission to hospital, COVID-19 result, organ support (respiratory, cardiovascular or renal), and death, by record review at 30 days. Mean age was 58.4 years, 11200 (50.4%) were female and 11034 (49.6%) male. Adults (age >16 years) were acutely unwell (median NEWS2 score of 4), frequently had limited performance status (46.9%) and had high rates of admission (67.1%), COVID-19 positivity (31.2%), organ support (9.8%) and death (15.5%). Children had much lower rates of admission (27.4%), COVID-19 positivity (1.2%), organ support (1.4%) and death (0.3%). Similar numbers of men and women presented to the ED, but men were more likely to be admitted (72.9% v 61.4%), require organ support (12.2% v 7.7%) and die (18.2% v 13.0%). Black or Asian adults tended to be younger than White adults (median age 54, 50 and 67 years), were less likely to have impaired performance status (43.1%, 26.8% and 51.6%), be admitted to hospital (60.8%, 57.3%, 69.6%) or die (11.6%, 11.2%, 16.4%), but were more likely to require organ support (15.9%, 14.3%, 8.9%) or have a positive COVID-19 test (40.8%, 42.1%, 30.0%). Adults admitted with suspected and confirmed COVID-19 had similar age, performance status and comorbidities (except chronic lung disease) to those who did not have COVID-19 confirmed, but were much more likely to need organ support (22.2% v 8.9%) or die (32.1% v 15.5%).
Important differences exist between patient groups presenting to the emergency department with suspected COVID-19. Adults and children differ markedly and require different approaches to emergency triage. Admission and adverse outcome rates among adults suggest that policies to avoid unnecessary ED attendance achieved their aim. Subsequent COVID-19 confirmation confers a worse prognosis and greater need for organ support.
ISRCTN registry, ISRCTN56149622, http://www.isrctn.com/ISRCTN28342533.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Without surgical repair, flexor tendon injuries do not heal and patients' ability to bend fingers and grip objects is impaired. However, flexor tendon repair surgery also requires optimal ...rehabilitation. There are currently three custom-made splints used in the rehabilitation of zone I/II flexor tendon repairs, each with different assumed harm/benefit profiles: the dorsal forearm and hand-based splint (long), the Manchester short splint (short), and the relative motion flexion splint (mini). There is, however, no robust evidence as to which splint, if any, is most clinical or cost effective. The Flexor Injury Rehabilitation Splint Trial (FIRST) was designed to address this evidence gap.
FIRST is a parallel group, superiority, analyst-blind, multi-centre, individual participant-randomised controlled trial. Participants will be assigned 1:1:1 to receive either the long, short, or mini splint. We aim to recruit 429 participants undergoing rehabilitation following zone I/II flexor tendon repair surgery. Potential participants will initially be identified prior to surgery, in NHS hand clinics across the UK, and consented and randomised at their splint fitting appointment post-surgery. The primary outcome will be the mean post-randomisation score on the patient-reported wrist and hand evaluation measure (PRWHE), assessed at 6, 12, 26, and 52 weeks post randomisation. Secondary outcome measures include blinded grip strength and active range of movement (AROM) assessments, adverse events, adherence to the splinting protocol (measured via temperature sensors inserted into the splints), quality of life assessment, and further patient-reported outcomes. An economic evaluation will assess the cost-effectiveness of each splint, and a qualitative sub-study will evaluate participants' preferences for, and experiences of wearing, the splints. Furthermore, a mediation analysis will determine the relationship between patient preferences, splint adherence, and splint effectiveness.
FIRST will compare the three splints with respect to clinical efficacy, complications, quality of life and cost-effectiveness. FIRST is a pragmatic trial which will recruit from 26 NHS sites to allow findings to be generalisable to current clinical practice in the UK. It will also provide significant insights into patient experiences of splint wear and how adherence to splinting may impact outcomes.
ISRCTN: 10236011.
There are few effective interventions for dementia.
To determine the clinical effectiveness and cost-effectiveness of an intervention to promote self-management, independence and self-efficacy in ...people with early-stage dementia.
To undertake a randomised controlled trial of the Journeying through Dementia intervention compared with usual care, conduct an internal pilot testing feasibility, assess intervention delivery fidelity and undertake a qualitative exploration of participants' experiences.
A pragmatic two-arm individually randomised trial analysed by intention to treat.
A total of 480 people diagnosed with mild dementia, with capacity to make informed decisions, living in the community and not participating in other studies, and 350 supporters whom they identified, from 13 locations in England, took part.
Those randomised to the Journeying through Dementia intervention (
= 241) were invited to take part in 12 weekly facilitated groups and four one-to-one sessions delivered in the community by secondary care staff, in addition to their usual care. The control group (
= 239) received usual care. Usual care included drug treatment, needs assessment and referral to appropriate services. Usual care at each site was recorded.
The primary outcome was Dementia-Related Quality of Life score at 8 months post randomisation, with higher scores representing higher quality of life. Secondary outcomes included resource use, psychological well-being, self-management, instrumental activities of daily living and health-related quality of life.
Participants were randomised in a 1 : 1 ratio. Staff conducting outcome assessments were blinded.
Outcome measures were administered in participants' homes at baseline and at 8 and 12 months post randomisation. Interviews were conducted with participants, participating carers and interventionalists.
The mean Dementia-Related Quality of Life score at 8 months was 93.3 (standard deviation 13.0) in the intervention arm (
= 191) and 91.9 (standard deviation 14.6) in the control arm (
= 197), with a difference in means of 0.9 (95% confidence interval -1.2 to 3.0;
= 0.380) after adjustment for covariates. This effect size (0.9) was less than the 4 points defined as clinically meaningful. For other outcomes, a difference was found only for Diener's Flourishing Scale (adjusted mean difference 1.2, 95% confidence interval 0.1 to 2.3), in favour of the intervention (i.e. in a positive direction). The Journeying through Dementia intervention cost £608 more than usual care (95% confidence interval £105 to £1179) and had negligible difference in quality-adjusted life-years (-0.003, 95% confidence interval -0.044 to 0.038). Therefore, the Journeying through Dementia intervention had a mean incremental cost per quality-adjusted life-year of -£202,857 (95% confidence interval -£534,733 to £483,739); however, there is considerable uncertainty around this. Assessed fidelity was good. Interviewed participants described receiving some benefit and a minority benefited greatly. However, negative aspects were also raised by a minority. Seventeen per cent of participants in the intervention arm and 15% of participants in the control arm experienced at least one serious adverse event. None of the serious adverse events were classified as related to the intervention.
Study limitations include recruitment of an active population, delivery challenges and limitations of existing outcome measures.
The Journeying through Dementia programme is not clinically effective, is unlikely to be cost-effective and cannot be recommended in its existing format.
Research should focus on the creation of new outcome measures to assess well-being in dementia and on using elements of the intervention, such as enabling enactment in the community.
This trial is registered as ISRCTN17993825.
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in
; Vol. 26, No. 24. See the NIHR Journals Library website for further project information.
The mainstay of treatment for diabetic peripheral neuropathic pain is pharmacotherapy, but the current National Institute for Health and Care Excellence guideline is not based on robust evidence, as ...the treatments and their combinations have not been directly compared.
To determine the most clinically beneficial, cost-effective and tolerated treatment pathway for diabetic peripheral neuropathic pain.
A randomised crossover trial with health economic analysis.
Twenty-one secondary care centres in the UK.
Adults with diabetic peripheral neuropathic pain with a 7-day average self-rated pain score of ≥ 4 points (Numeric Rating Scale 0-10).
Participants were randomised to three commonly used treatment pathways: (1) amitriptyline supplemented with pregabalin, (2) duloxetine supplemented with pregabalin and (3) pregabalin supplemented with amitriptyline. Participants and research teams were blinded to treatment allocation, using over-encapsulated capsules and matching placebos. Site pharmacists were unblinded.
The primary outcome was the difference in 7-day average 24-hour Numeric Rating Scale score between pathways, measured during the final week of each pathway. Secondary end points included 7-day average daily Numeric Rating Scale pain score at week 6 between monotherapies, quality of life (Short Form questionnaire-36 items), Hospital Anxiety and Depression Scale score, the proportion of patients achieving 30% and 50% pain reduction, Brief Pain Inventory - Modified Short Form items scores, Insomnia Severity Index score, Neuropathic Pain Symptom Inventory score, tolerability (scale 0-10), Patient Global Impression of Change score at week 16 and patients' preferred treatment pathway at week 50. Adverse events and serious adverse events were recorded. A within-trial cost-utility analysis was carried out to compare treatment pathways using incremental costs per quality-adjusted life-years from an NHS and social care perspective.
A total of 140 participants were randomised from 13 UK centres, 130 of whom were included in the analyses. Pain score at week 16 was similar between the arms, with a mean difference of -0.1 points (98.3% confidence interval -0.5 to 0.3 points) for duloxetine supplemented with pregabalin compared with amitriptyline supplemented with pregabalin, a mean difference of -0.1 points (98.3% confidence interval -0.5 to 0.3 points) for pregabalin supplemented with amitriptyline compared with amitriptyline supplemented with pregabalin and a mean difference of 0.0 points (98.3% confidence interval -0.4 to 0.4 points) for pregabalin supplemented with amitriptyline compared with duloxetine supplemented with pregabalin. Results for tolerability, discontinuation and quality of life were similar. The adverse events were predictable for each drug. Combination therapy (weeks 6-16) was associated with a further reduction in Numeric Rating Scale pain score (mean 1.0 points, 98.3% confidence interval 0.6 to 1.3 points) compared with those who remained on monotherapy (mean 0.2 points, 98.3% confidence interval -0.1 to 0.5 points). The pregabalin supplemented with amitriptyline pathway had the fewest monotherapy discontinuations due to treatment-emergent adverse events and was most commonly preferred (most commonly preferred by participants: amitriptyline supplemented with pregabalin, 24%; duloxetine supplemented with pregabalin, 33%; pregabalin supplemented with amitriptyline, 43%;
= 0.26). No single pathway was superior in cost-effectiveness. The incremental gains in quality-adjusted life-years were small for each pathway comparison amitriptyline supplemented with pregabalin compared with duloxetine supplemented with pregabalin -0.002 (95% confidence interval -0.011 to 0.007) quality-adjusted life-years, amitriptyline supplemented with pregabalin compared with pregabalin supplemented with amitriptyline -0.006 (95% confidence interval -0.002 to 0.014) quality-adjusted life-years and duloxetine supplemented with pregabalin compared with pregabalin supplemented with amitriptyline 0.007 (95% confidence interval 0.0002 to 0.015) quality-adjusted life-years and incremental costs over 16 weeks were similar amitriptyline supplemented with pregabalin compared with duloxetine supplemented with pregabalin -£113 (95% confidence interval -£381 to £90), amitriptyline supplemented with pregabalin compared with pregabalin supplemented with amitriptyline £155 (95% confidence interval -£37 to £625) and duloxetine supplemented with pregabalin compared with pregabalin supplemented with amitriptyline £141 (95% confidence interval -£13 to £398).
Although there was no placebo arm, there is strong evidence for the use of each study medication from randomised placebo-controlled trials. The addition of a placebo arm would have increased the duration of this already long and demanding trial and it was not felt to be ethically justifiable.
Future research should explore (1) variations in diabetic peripheral neuropathic pain management at the practice level, (2) how OPTION-DM (Optimal Pathway for TreatIng neurOpathic paiN in Diabetes Mellitus) trial findings can be best implemented, (3) why some patients respond to a particular drug and others do not and (4) what options there are for further treatments for those patients on combination treatment with inadequate pain relief.
The three treatment pathways appear to give comparable patient outcomes at similar costs, suggesting that the optimal treatment may depend on patients' preference in terms of side effects.
The trial is registered as ISRCTN17545443 and EudraCT 2016-003146-89.
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme, and will be published in full in
; Vol. 26, No. 39. See the NIHR Journals Library website for further project information.
Social emotional development in infancy is a predictor of outcomes in later life, yet there is little evidence of effectiveness for parenting interventions designed to enhance social emotional ...wellbeing in infancy. An 18-month two-arm randomized controlled pilot trial evaluated the feasibility of a definitive trial of Incredible Years (IY) Infant and Toddler parent programs delivered in a proportionate universal model, called Enhancing Social-Emotional Health and Wellbeing in the Early Years (E-SEE) Steps. Intervention families received an IY Babies book (universal dose), followed by the IY Infant and/or the Toddler group-based programs, based on parent depression (PHQ-9) and/or child social emotional development (ASQ:SE-2) scores. Control parents received services as usual. Parents from two English local authorities with a child eight-weeks-old or younger participated, and were block randomized using a web-based system. Primary endpoints for the study were feasibility parameters relating to recruitment, retention, intervention fidelity and appropriateness of measures. 205 participants were randomized (152:53, intervention:control). Our target was 288 parents. Trial retention rate was higher than expected, with a completion rate of 88% (n = 181, 137:44) at follow-up 3; equating to 94% of 192 expected participants. Intervention uptake was lower than expected. Fidelity of delivery was acceptable and measures were deemed appropriate. A definitive trial is feasible with design amendments to include: introduction of a child screener for intervention eligibility; enhanced intervention material; revised sample size and random allocation ratio. Our internal pilot became an external pilot due to these changes.
Highlights
This is the first pilot of a proportionate universal delivery of the IY parent program.
Trial retention was high at 88% at final follow-up (18 months post baseline).
Emerging findings suggest a definitive trial of E-SEE STEPS is warranted.
Definitive trials should consider methods to enhance intervention uptake.
Trials should consider intervention compliance with relevant guidelines.
The number of people with diabetes is growing rapidly. Diabetes can cause nerve damage leading to severe pain in the feet, legs and hands, which is known as diabetic peripheral neuropathic pain ...(DPNP). In the UK, the National Institute for Health and Care Excellence (NICE) recommends amitriptyline, duloxetine, pregabalin or gabapentin as initial treatment for DPNP. If this is not effective, adding one of the other drugs in combination with the first is recommended. NICE points out that these recommendations are not based on robust evidence. The OPTION-DM randomised controlled trial has been designed to address this evidence deficit, with the aims of determining the most clinically beneficial, cost-effective and tolerated treatment pathway for patients with DPNP.
A multicentre, double-blind, centre-stratified, multi-period crossover study with equal allocation to sequences (1:1:1:1:1:1) of treatment pathways. Three hundred and ninety-two participants will be recruited from secondary care DPNP centres in the UK. There are three treatment pathways: amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline and duloxetine supplemented with pregabalin. All participants will receive all three pathways and randomisation will determine the order in which they are received. The primary outcome is the difference between 7-day average 24-h pain scores on an 11-point NRS scale measured during the final follow-up week of the treatment pathway. Secondary outcomes for efficacy, cost-effectiveness, safety, patient-perceived tolerability and subgroup analysis will be measured at week 6 and week 16 of each pathway.
The study includes direct comparisons of the mainstay treatment for DPNP. This novel study is designed to examine treatment pathways and capture clinically relevant outcomes which will make the results generalisable to current clinical practice. The study will also provide information on health economic outcomes and will include a subgroup study to provide information on whether patient phenotypes predict response to treatment.
ISRCTN17545443 . Registered on 12 September 2016.
Asthma episodes and deaths are known to be seasonal. A number of reports have shown peaks in asthma episodes in school-aged children associated with the return to school following the summer ...vacation. A fall in prescription collection in the month of August has been observed, and was associated with an increase in the number of unscheduled contacts after the return to school in September.
The primary objective of the study was to assess whether or not a NHS-delivered public health intervention reduces the September peak in unscheduled medical contacts.
Cluster randomised trial, with the unit of randomisation being 142 NHS general practices, and trial-based economic evaluation.
Primary care.
A letter sent (
= 70 practices) in July from their general practitioner (GP) to parents/carers of school-aged children with asthma to remind them of the importance of taking their medication, and to ensure that they have sufficient medication prior to the start of the new school year in September. The control group received usual care.
The primary outcome measure was the proportion of children aged 5-16 years who had an unscheduled medical contact in September 2013. Supporting end points included the proportion of children who collected prescriptions in August 2013 and unscheduled contacts through the following 12 months. Economic end points were quality-adjusted life-years (QALYs) gained and costs from an NHS and Personal Social Services perspective.
There is no evidence of effect in terms of unscheduled contacts in September. Among children aged 5-16 years, the odds ratio (OR) was 1.09 95% confidence interval (CI) 0.96 to 1.25 against the intervention. The intervention did increase the proportion of children collecting a prescription in August (OR 1.43, 95% CI 1.24 to 1.64) as well as scheduled contacts in the same month (OR 1.13, 95% CI 0.84 to 1.52). For the wider time intervals (September-December 2013 and September-August 2014), there is weak evidence of the intervention reducing unscheduled contacts. The intervention did not reduce unscheduled care in September, although it succeeded in increasing the proportion of children collecting prescriptions in August as well as having scheduled contacts in the same month. These unscheduled contacts in September could be a result of the intervention, as GPs may have wanted to see patients before issuing a prescription. The economic analysis estimated a high probability that the intervention was cost-saving, for baseline-adjusted costs, across both base-case and sensitivity analyses. There was no increase in QALYs.
The use of routine data led to uncertainty in the coding of medical contacts. The uncertainty was mitigated by advice from a GP adjudication panel.
The intervention did not reduce unscheduled care in September, although it succeeded in increasing the proportion of children both collecting prescriptions and having scheduled contacts in August. After September there is weak evidence in favour of the intervention. The intervention had a favourable impact on costs but did not demonstrate any impact on QALYs. The results of the trial indicate that further work is required on assessing and understanding adherence, both in terms of using routine data to make quantitative assessments, and through additional qualitative interviews with key stakeholders such as practice nurses, GPs and a wider group of children with asthma.
Current Controlled Trials ISRCTN03000938.
This project was funded by the NIHR Health Technology Assessment programme and will be published in full in
; Vol. 20, No. 93. See the HTA programme website for further project information.
Some text in this abstract has been reproduced from Lindsay J, Din S, Hawkey C, Hind D, Irving P, Lobo A, et al. OFR-9 An RCT of autologous stem-cell transplantation in treatment refractory Crohn’s ...disease (low-intensity therapy evaluation): ASTIClite. Gut 2021; 70 (Suppl. 4):A4. Background Treatment-refractory Crohn’s disease is characterised by chronic symptoms, poor quality of life and high costs to the NHS, and through days of work lost by patients. A previous trial of autologous haematopoietic stem cell transplant (HSCT) failed its end point of medication-free clinical remission for 3 months with no evidence of disease activity, and reported high toxicity. Subsequent studies suggest that HSCT achieves complete mucosal healing in 50% of patients, and that toxicity likely relates to the cyclophosphamide dose. Objectives The primary objective was to assess the efficacy of HSCTlite (HSCT with low-dose cyclophosphamide) compared with standard care for inducing regression of intestinal ulceration in patients with refractory Crohn’s disease at week 48. Secondary objectives included the assessment of disease activity, quality of life and regimen safety. Mechanistic objectives included immune reconstitution after HSCTlite. Design Two-arm, parallel-group randomised controlled trial with a 2 : 1 (intervention : control) allocation ratio. Setting Nine NHS trusts (eight trusts were recruitment sites; one trust was a treatment-only site). Participants Adults with treatment-refractory Crohn’s disease, for whom surgery was inappropriate or who had declined surgery. Interventions The intervention treatment was HSCTlite using cyclophosphamide, and the control was any current available treatment for Crohn’s disease, apart from stem cell transplantation. Main outcomes The primary outcome was treatment success at week 48 mucosal healing (Simple Endoscopic Score for Crohn’s Disease ulcer subscore of 0) without surgery or death, assessed by central readers blinded to allocation and timing of assessment. Key secondary outcomes were clinical remission, Simple Endoscopic Score for Crohn’s Disease scores at week 48, change in Crohn’s Disease Activity Index scores and safety. Results The trial was halted owing to Suspected unexpected serious adverse events that took place after randomising 23 patients (HSCTlite arm, n = 13; usual-care arm, n = 10). Ten out of the 13 patients randomised to the HSCTlite arm received the intervention and nine (one death) reached the 48-week follow-up. In the usual-care arm 9 out of the 10 patients randomised reached the 48-week follow-up (one ineligible). The primary outcome was available for 7 out of 10 HSCTlite patients (including the patient who died) and six out of nine usual-care patients. Absence of endoscopic ulceration without surgery or death was reported in three out of seven (43%) HSCTlite patients, compared with zero out of six (0%) usual-care patients. Centrally read Simple Endoscopic Score for Crohn’s Disease scores mean (standard deviation) were 10.8 (6.3) and 10.0 (6.1) at baseline, compared with 2.8 (2.9) and 18.7 (9.1) at week 48, in the HSCT and usual-care arms, respectively. Clinical remission (Crohn’s Disease Activity Index scores of < 150) occurred in 57% and 17% of patients in the HSCTlite and usual-care arms, respectively, at week 48. Serious adverse events were more frequent in the HSCTlite arm 38 in 13 (100%) patients than in the usual-care arm 16 in 4 (40%) patients. Nine suspected unexpected serious adverse reactions were reported in six HSCTlite patients, including three cases of delayed renal failure due to proven thrombotic microangiopathy. Two HSCTlite patients died. Conclusions Within the limitations of reduced patient recruitment and numbers of patients assessed, HSCTlite meaningfully reduced endoscopic disease activity, with three patients experiencing resolution of ulceration. Suspected unexpected serious adverse reactions, particularly relating to thrombotic microangiopathy, make this regimen unsuitable for future clinical use. Limitations The early trial closure prevented complete recruitment, and the impact of the coronavirus pandemic prevented completion of some study investigations. Small participant numbers meant analysis could only be descriptive. Future work Owing to undetermined aetiology of thrombotic microangiopathy, further trials of HSCTlite in this population are not considered appropriate. Priorities should be to determine optimal treatment strategies for patients with refractory Crohn’s disease, including those with a stoma or multiple previous resections. Trial registration This trial is registered as ISRCTN17160440 and EudraCT 2017-002545-30. Funding This award was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) partnership. This is published in full in Efficacy and Mechanism Evaluation ; Vol. 11, No. 3. See the NIHR Funding and Awards website for further award information.
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